1. Field of the Invention
The invention relates to a method and apparatus for manufacturing biochips; in particular, the invention relates to a method and apparatus for mass producing biochips with a high-density array of reagents disposed thereupon.
2. Description of the Related Art
Advances in industries employing chemical and biological processes have created a need for devices that accurately and automatically dispense small quantities of liquids containing chemically or biologically active substances for commercial or experimental use. Accuracy and precision in the amount of liquid dispensed is important both from the standpoint of causing a desired reaction and minimizing the amount of material used. An example of a device with an array of reagents disposed thereupon is a biochip.
FIG. 1 is a schematic flow representation of a system for producing a biochip according to U.S. Pat. No. 6,001,309. In FIG. 1, a storage subsystem 300 is shown as an array of racks. Each bin in the rack contains an array of storage well plates 302. A master controller 304 controls the system. Under computer signal, one or more plates 302 are conveyed from the storage area 300 to the next station 306. At the station 306 a robotic arm 308 is under the control of subsystem controller 309. The robotic arm 308 using micropipette tips 310 transfers microliter quantities of liquid from the plate 302 to one or more appropriate jet to-be-filled 312 located at a maintenance and fill station under the control of subsystem controller 315. For reusable jetting devices, the maintenance and fill station has maintenance caps 316. A holder 318 positions the jetting device 312 on a translation bar 320; thereby, the jetting device 312 is moved to the test station 322 under the control of subsystem controller 323. If the jetting device 312 passes the test station, it is then moved by means of the translation bar 320 to the jetting position 334 and positioned over the substrate 336 by means of the translation bar 320 and the holder 318. The jetting dispenser is now in position to begin jetting drops to create the biochip.
FIG. 2a and FIG. 2b show another conventional dispensing apparatus 108 disclosed in U.S. Pat. No. 6,063,339. The dispensing apparatus 108 generally comprises a dispensing head 128 having a dispensing means 204 operated by an actuator. The dispensing head 108 is mounted on an X-Y table 110, including position stepper motor 123, 124 that are operable to move the dispensing head 128 and the table 112. A syringe pump 120 is hydraulically coupled to a fluid reservoir 116 through a first one-way check valve 145. The syringe pump 120 draws fluid 130 from the fluid reservoir 116 and provides it to the dispensing head 128 through a second check valve 145. The syringe pump 120 is operated by a syringe pump driver 142 for extending and retracting the piston 118 within the syringe barrel 362. When the piston 118 is extended, reagent 130 is forced to flow from the syringe barrel 362 into the dispensing head 128 via the supply tube, whereupon it is ejected by the dispensing head 128 onto the substrate 111 in the form of droplets. A controller 114 oversees operation of the pump 120, X-Y table 110, and the dispensing head 128.
FIG. 2b shows a schematic view of a substrate 111. The substrate 111 is divided into rows 714 and columns 716 having a predetermined resolution in terms of a number of addressable target areas 706 per linear distance. Upon executing a first linear pass 730 along a first row, the dispensing head reverses direction and executes a second pass 734 along an adjacent second row. Such bi-directional dispensing advantageously decreases the time required to complete a dispensing operation in comparison to a unidirectional dispensing operation.
Since the chemical and biological analysis are rapidly growing fields, mass production of biochips is required. However, since the system disclosed in U.S. Pat. No. 6,001,309 is provided with only one jetting device, it actuates only one dispenser at a time. Thus, the manufacturing efficiency of the biochips is low.
Similarly, in the method cited from U.S. Pat. No. 6,063,339, since only one substrate is placed on the table, only one biochip can be made at a time. Thus, this method is not adapted for mass production.